Project Summary/Abstract The goal of neonatal intensive care unit (NICU) care is not just survival of preterm infants, but also intact neurodevelopment for these vulnerable patients. Many factors affect neurodevelopment. Identification of factors that are modifiable at a time point early enough to improve the developmental trajectory of an individual infant is needed. While preterm infants are discharged from the NICU with a certain developmental potential based on their gestational age and clinical course, socioeconomic status (SES) of the home environment can significantly alter the developmental trajectory. Poverty increases risk for neurodevelopmental deterioration, resulting in significant health disparities. The means by which poverty alters neurodevelopment are unknown. The microbiome is influenced by environment and in turn influences brain development. We hypothesize that that the microbiome is a biologic effector of the influence of SES and environment on neurodevelopment. This proposal will focus on two key time points at which the microbiome is exposed to significant environmental alteration ? first 2 weeks of life in the NICU and 6-12 months of life in the home environment. Longitudinal clinical data, patient microbial samples, environmental data, and SES data will be collected on established cohorts of preterm infants from five institutions across the United States already investigating the intestinal microbiome of preterm infants. Neurodevelopmental exams will be performed to assess the functional outcome of school readiness. The goal of this proposal is to demonstrate that microbiome development influences neurodevelopment. Furthermore we will identify environmental factors associated with SES that influence the microbiome and thus neurodevelopmental outcomes. Strengths of this proposal include distinctive expertise of the interdisciplinary investigative team in neonatal care, neurodevelopment, microbiome analysis, bioinformatics, economics, and analysis of environmental features of the home environment. Advanced sequencing techniques, spatial analysis of environmental factors (geomapping), and economic modeling will be used to investigate the relationships among SES, environment, microbiome, and neurodevelopmental outcome to identify a time point and possible environmental or microbiome modification to improve outcomes. Beyond increasing social strategies, expanding effective learning models, and mitigating medical needs of at risk infants, understanding and promoting shifts in the microbiome could lead to improved understanding of health disparities and enable interventions to alter infant neurodevelopmental-trajectories in innovative ways.